The present invention more particularly relates to a production process for a multilayer composite, in which one or more layers are firstly applied to a substrate by coating using a liquid component, the coated multilayer composite is dried thereafter and the dried multilayer composite is thereafter rolled up. The final step in the process is the cleaning of the installation, which, according to the invention, is carried out by means of a CIP system, i.e. by means of a system allowing “cleaning in place”, that is integrated into the installation. The invention also relates to the use of the multilayer composite produced according to the process according to the invention as a transdermal system for the application of pharmaceutical active ingredients and the application of e.g. cosmetic active ingredients, pharmaceutical active ingredients, food supplements or medical products in body cavities.
In addition to the known forms of application for drugs such as tablets, capsules, sugar-coated tablets, drops, injections or rectal forms of application, there also is the dosage form by means of transdermal systems or wafers. Transdermal systems and wafers are produced from web-shaped materials, with the production of the web-shaped materials comprising a plurality of successive steps such as coating, drying and rolling onto rollers. By way of example, they are described in WO 03/61635. Cleaning the installation as a final work step during operation usually follows the actual procedure of production. This is because the installation should be available as quickly as possible for the production of another, new recipe in order to avoid uneconomical downtime. Furthermore, it should be possible to reliably validate the cleaning process.
During the step of coating, one or more liquid components are applied to a substrate by means of a coating installation. However, the multilayer composite, whose coating is complete after this, still contains a relatively high proportion of liquid, which is usually removed by heat in the next successive production step.
The multilayer composite with a completed coating is therefore fed into a drying oven for drying, the latter preferably being operated in continuous operation. The drying oven can comprise one or more drying zones. The individual drying zones are different in terms of their respectively differing temperatures and amounts of air. Additionally, each drying zone should possess its own air control, into which filter and heating elements are usually integrated as well. The action of the heat in the drying oven on the coated multilayer composite allows the humidity from the coated multilayer composite to escape into the airflow. In order to keep the humidity in the airflow stable, dry fresh air has to be supplied, and it is used to replace the used up, damp air. Variations in the humidity of the fresh air supply have a direct impact on the efficiency of the drying and an indirect impact on the quality of the finished product, which should not be too damp, but not too dry either.
The dried multilayer composite emerging from the drying oven is immediately rolled onto rollers.
While the multilayer composite, which has finished drying and is rolled up, is optionally put into temporary storage or transported away, the next step of operation is the complete cleaning of the installation, which should be carried out as quickly as possible, but, at the same time, should also be carried out so thoroughly that “cross contamination”, i.e. transmission of traces of contents of the material produced in the preceding production cycle in the installation to the material produced in the subsequent production cycle in the installation, can be reliably excluded. This particularly thorough cleaning process is also known as according to GMP guidelines in the terminology of the art (see Wikipedia, a free encyclopedia on the Internet). Combined therewith, the particularly uneconomical downtime of the installation should be shortened to the shortest possible time.